Chloroquine and COVID

“Doctors can now prescribe chloroquine for that off-label purpose of dealing with the symptoms of coronavirus,” Pence said. “The president’s very optimistic.”

Since clinical trial design and analysis is a thing I do, I thought I’d write about the chloroquine problem.

Chloroquine and the related hydroxychloroquine are anti-malarial drugs, which are also used in some autoimmune diseases.  They are inexpensive and their risks are well understood, with chloroquine having been used to prevent and treat malaria for many years.  They’re safe-ish at the standard doses^*: they have unpleasant side-effects, but not nearly as unpleasant as malaria.  Also, they’ve been found to have anti-viral effects in lab studies, including against SARS, so they might just work in treatment or prevention of COVID-19.

You might wonder how a malaria drug would work on a virus.  I will quote a pharmaceutical chemist, Derek Lowe

So if you see someone confidently explaining just how chloroquine exerts whatever antiviral activity it may have, feel free to go read something else. No one’s sure yet.

Now, you wouldn’t expect the President of the United States to be up on candidate antiviral treatments for SARS, so why was he very optimistic?

A small study in France gave hydroxychloroquine to 26 people with COVID-19, and didn’t give it to 16 others — this wasn’t randomised, it’s just how things turned out.  Of the 26 people getting hydroxychloroquine, 14 were virus-free after 6 days. The study reported this as 70%, because 6 of the other 12 people had dropped out for various reasons, including one death.   Normally, you’d report it as 14/26, or 54% — either that or do some more complicated analyses.   A subset of at least 6 of the people getting hydroxychloroquine also got the antibiotic azithromycin (they don’t say how many — could be anything from 6 to 12). Of these people, 6 became virus-free, which they reported as 100%.

This study is encouraging, but the fact that it’s not randomised and is very small and didn’t report results for nearly a quarter of the treated people mean that it’s no more than that. It’s a good reason to do a randomised trial that’s large enough and well-designed enough to convince people which ever way it turns out. That’s happening: the WHO is running a trial of four potential treatments, which is designed to be simple enough that even an over-worked and under-resourced hospital system can take part.  The trial design also allows for changes if new treatments or new information about existing treatments emerges.

As I’ve mentioned before, there are lots of small studies being done around the world.  In particular, the Journal of Zhejiang University just published a small randomised trial of hydroxychloroquine.  I learned about it from Dr Mel Thompson, who was quoted in a Forbes post about the trial, by Tara Haelle.  In this study 15 people were given hydroxychloroquine and 15 got the standard care.  This trial is too small to say much, 13 of the treated group and 14 of the control group were virus-free after 7 days, and the results for other measurements were also not too different.   The trial results are consistent with the drug having no effect. But they’re also consistent with the drug having a big effect.

At the moment, some people are getting various treatments and others aren’t, mostly in a haphazard way.  If it were done with randomisation and reliable basic data collection, we might save a lot of lives. At worst, we’d know what didn’t work.

^* Yes, one person died and one was hospitalised in the US from taking chloroquine, but they don’t seem to have known anything about the usual doses, which matters when the fish-tank version of the product comes in large packets.